G protein-coupled receptors (GPCRs) regulate virtually all known physiological processes and are a premier class of drug targets.  However, a detailed mechanistic understanding of their complex activation mechanisms has been hindered by the difficulty of expressing and purifying these membrane proteins.  We will describe how mammalian expression provides a versatile platform for high-level GPCR expression.  In addition, we will discuss how new expression technologies can address the challenges that have previously limited the scope of mammalian expression systems for biochemical and biophysical studies of GPCRs.